Nipah virus infection is an emerging new disease of humans and swine, first described during a 1998-1999 epidemic in Malaysia. The Nipah virus causes encephalitis in humans and respiratory and central nervous system disease in swine and other animals. This virus and the related Hendra virus are paramyxoviruses that are distinct from any of the other established genera of paramyxoviruses and have been proposed to represent members of a new genus (Henipavirus). There have been no reports of attempts to develop and evaluate vaccines against this newly discovered group of viruses, which are capable of causing fatal encephalitis in man and animals. The long-term objective of this project is to develop a live canarypox virus vector expressing the F and G proteins of the Nipah virus for use as a vaccine to control Nipah virus infection in man and animals. A second objective is to develop a serologic diagnostic assay for Nipah virus infection, which can be performed under biosafety level 2 (BSL2) conditions. Current diagnostic assays require growing the Nipah virus under BSL4 conditions. The pig will be used as the animal model for testing the safety and efficacy of the canarypox vectored vaccine. This is appropriate because the pig is very susceptible to infection with Nipah virus and because in the Malaysian outbreak humans contracted Nipah virus infection from infected pigs. The canarypox vector has been successfully used as a vaccine in humans, pigs and other animals. Vaccinated pigs should develop neutralizing antibodies and memory T cells to the Nipah F and G proteins. Pigs that become infected with Nipah virus will also develop antibodies against the nucleocapsid (N) protein. Antibodies to N can be detected with an ELISA assay using the N protein expressed in a baculovirus vector as the antigen. This would allow for the rapid identification of vaccinated or unvaccinated pigs, which become infected with the wild type virus. A vaccine and companion diagnostic test with these attributes would be very useful in future eradication programs by reducing infection in pigs, thereby reducing transmission to other pigs and humans and reducing the social, economic, and environmental impact of the disease. Since Nipah and Hendra viruses are closely related, this work will provide important information relative to the potential for development of safe and effective vaccines for humans against members of this novel group of emerging zoonotic paramyxovirus.